The invention relates to the lining of bodily stents.
Angioplasty, which involves the insertion of a catheter, e.g., a balloon catheter, into a blood vessel to expand an occluded region of the blood vessel, is frequently used to treat arteriosclerosis. Restenosis, or closing of the vessel, is a process that may occur following angioplasty. This process may be characterized by the proliferation of smooth muscle cells stimulated by the angioplasty treatment. Restenosis may also occur as a result of clot formation following angioplasty, due to injury to the vessel wall which triggers the natural clot-forming cascade of the blood.
A number of different approaches have been taken to prevent post-angioplasty vessel reclosure. One such approach has been the placement of a medical prosthesis, e.g., an intravascular metal stent, to mechanically keep the lumen open. For example, an intravascular stent made of an expandable stainless steel wire mesh tube has been used to prevent post angioplasty restenosis and vessel reclosure. The stent may be formed of wire configured into a tube and is usually delivered into the body lumen using a catheter. The catheter carries the prosthesis in a reduced-size form to the desired site. When the desired location is reached, the prothesis is released from the catheter and expanded so that it engages the lumen wall. Stents are typically fabricated from metals, alloys, or plastics and remain in the blood vessel indefinitely.
The invention features a catheter assembly for delivering a stent to a body lumen and lining the stent with a hydrogel to reduce shear forces and flow disturbances in the blood, protect damaged cells adjacent to the stent, reduce platelet deposition at the stent site, and/or deliver a drug to reduce or prevent restenosis of stented lumens. The assembly includes a catheter which has a balloon at least a portion of which is coated with a hydrogel. The assembly also includes an expansible stent mounted on the balloon in a contracted condition for passage with the catheter to a site of a body lumen. Expansion of the balloon lodges the stent in the body lumen with the hydrogel deposited on an inner surface of the stent as a lining. The hydrogel may be crosslinked to form a relatively permanent lining on the inner surfaces of the stent or left uncrosslinked to form a relatively degradable lining on the inner surfaces of the stent. Preferably, the longevity of a crosslinked form of a given hydrogel as a stent lining is at least twice that of its uncrosslinked form.
The hydrogel is selected from the group consisting of a polyacid, e.g., a poly(acrylic acid) or a polycarboxylic acid, cellulosic polymer, collagen, gelatin, albumin, alginate, poly 2-hydroxy ethyl methyl acrylate (HEMA), polyvinylpyrrolidone, maleic anhydride polymer, polyamide, polyacrylamide, polyvinyl alcohol, polyethylene glycol, polyethylene oxide, and polysaccharide, e.g., a mucopolysaccharide such as hyaluronic acid. For example, the hydrogel may be a poly(acrylic acid), e.g., CARBOPOL(copyright) 941 poly (acrylic acid) (B F Goodrich), in a crosslinked or uncrosslinked form.
In some cases, the hydrogel may be crosslinked prior to lining the stent. For example, the hydrogel coating on a balloon may be contacted with a primer dip before the hydrogel is deposited onto the inner surfaces of a stent. Alternatively, the hydrogel lining may be contacted with a crosslinking agent in situ, i.e., the balloon portion of the catheter with a coating of uncrosslinked hydrogel is inserted into the body and after the deployment of the stent in the body lumen and deposition of the hydrogel onto the inner surfaces of the stent, the hydrogel is contacted with a crosslinking agent.
The hydrogel may include a therapeutic agent, e.g., a drug, to reduce or prevent clotting and/or restenosis at the stent site. For example, the therapeutic agent may reduce or eliminate acute thrombosis of the stent and reduce in-stent restenosis or interfere with cell metabolism (e.g., an anti-metabolite), thereby killing undesired cells. The therapeutic agent may be an anti-platelet drug, anticoagulant drug, anti-metabolite drug, anti-angiogenic drug, or anti-proliferative drug. The therapeutic agent may be an anti-thrombogenic agent such as heparin, PPACK, enoxaprin, aspirin, and hirudin or a thrombolytic agent such as urokinase, streptokinase, and tissue plasminogen activator. The hydrogel may also include an agent which inhibits platelet deposition or smooth muscle cell proliferation. The agent may also be a nucleic acid which encodes a therapeutic protein, e.g., a naked nucleic acid or a nucleic acid incorporated into a viral vector or liposome. By naked nucleic acid is meant an uncoated single or double stranded DNA or RNA molecule not incorporated into a virus or liposome. Antisense oligonucleotides which specifically bind to complementary mRNA molecules and thereby reduce or inhibit protein expression can also be delivered to the stent site via the hydrogel coating on the balloon catheter. The drug may be incorporated into microspheres to prolong the time over which a delivered drug is released and minimize spreading of the delivered drug to non-target sites.
Rather than administering the hydrogel lining via a coating on a balloon, the catheter may include a delivery port for administering a hydrogel to the inner surfaces of the stent. For example, the balloon may include a first layer and a second outer apertured layer overlying the delivery port. The hydrogel is administered through the outer apertured layer of the balloon to contact the inner surfaces of the stent to create a lining therein. After the hydrogel is applied to the stent, a crosslinking agent may be administered to contact the hydrogel. For example, an aginate hydrogel can be crosslinked by contacting it with calcium gluconate, and a hyaluronic acid hydrogel can be crosslinked by contacting it with divinyl glycol.
Lining a stent using a porous balloon, e.g., a channeled balloon, is accomplished by deploying the stent positioned over the porous balloon and then infusing a hydrogel through the pores in the balloon to line the inner surfaces of the stent with a polymeric layer to facilitate smooth flow of blood through the stent. The hydrogel fills the interstices of a mesh stent creating a smooth lining inside the stent.
Alternatively, one or more delivery ports may be located proximal to the balloon over which the stent is mounted, i.e., upstream of the stent with respect to the blood flow, and the hydrogel administered via the delivery port and carried to the inner surfaces of the stent by the blood flow.
The invention also features a method for lining a stent which includes the steps of providing a catheter assembly including a balloon at least a portion of which is coated with a hydrogel over which is mounted an expansible stent in a contracted condition, introducing the assembly into a body lumen, and inflating the balloon to lodge the stent in the body lumen and to release the hydrogel from the coated portion of the balloon to the inner surfaces of the stent to create a lining. Preferably, the body lumen is a blood vessel, more preferably it is an artery, such as an artery occluded by an arteriosclerotic plaque.
Also within the invention is a method of lining a stent which has been previously deployed in a body lumen of a patient. The method includes the steps of providing a catheter including a balloon at least a portion of which is coated with a hydrogel, introducing the catheter into the body lumen, advancing the catheter in the body lumen until the balloon is positioned proximate to the inner surfaces of the stent, and inflating the balloon to release the hydrogel from the coated portion of the balloon to the inner surfaces of the stent to create a lining. The catheter may include a sheath over the hydrogel-coated portion of the balloon which is removed prior to inflating the balloon.
A previously-deployed stent may also be lined using a catheter which includes a balloon and delivery port, the balloon portion of which contains a first layer and a second outer aperatured layer overlying the delivery port. The method includes the steps of introducing the catheter into the body lumen, advancing the catheter in the body lumen until the outer aperatured layer is positioned proximate to the inner surfaces of the stent, delivering a hydrogel into a space between the first layer and the second outer aperatured layer, and inflating the balloon to press the hydrogel through the outer aperatured layer thereby depositing the hydrogel on the inner surfaces of the stent as a lining.
A previously-deployed permeable stent, e.g., an open mesh metal stent, in the region of a blood vessel affected by an aneurism may be selectively lined with a hydrogel to render the portion of the stent proximate to the aneurism impermeable, thereby preventing blood flow into the aneurism. By xe2x80x9cselectively liningxe2x80x9d is meant depositing a lining material, e.g., a hydrogel, in a desired region of the inner surface of a stent while leaving other regions of the inner surface of the stent free from the lining material. The hydrogel lining is delivered to the stent as a coating on a balloon portion of a catheter or via ports of a channeled balloon. For example, a method of selectively lining a permeable stent to treat an aneurism, includes the steps of providing a balloon catheter with at least a portion of the balloon coated with a hydrogel; introducing the catheter into an aneurismal blood vessel in which a permeable stent has previously been deployed in the region of the aneurism; advancing the catheter in the affected vessel until the coated portion is positioned proximate to the aneurism; and inflating the balloon to release the hydrogel from the coated portion to an inner surface of the stent proximate to the aneurism. The hydrogel lining renders the inner surface of the stent near the aneurism impermeable, thereby reducing or preventing blood flow into the aneurism, but permitting blood flow through the unlined portions of the stent to or from branching blood vessels in an area of the vessel unaffected by the aneurism.
Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims.